Anti-inflammatory compounds from Penicillium fungi: A review

Inflammation is a complex immune response that plays an important role in host defence but becomes dysregulated in many chronic diseases. This situation has increased attention toward the genus Penicillium, particularly endophytic species, which possess significant anti-inflammatory potential and represent a rich source of structurally diverse and pharmacologically active specialized metabolites. Therefore, this review comprehensively summarizes 385 specialized metabolites isolated from Penicillium fungi based on articles published from 2003 to 2025, with emphasis on their anti-inflammatory activities and underlying molecular mechanisms. The identified compounds belong to several structural classes, including meroterpenoids, sesquiterpenoids, diterpenoids, polyketides, alkaloids, and steroids. Most metabolites exhibited significant inhibitory effects on key pro-inflammatory mediators such as nitric oxide (NO), prostaglandin E₂ (PGE₂), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-stimulated macrophage and microglial cells. These activities are mainly associated with the regulation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signalling pathways. In addition, several metabolites demonstrated promising anti-inflammatory activity in both in vitro and in vivo studies. These findings highlight Penicillium endophytes as a prolific and sustainable reservoir of bioactive compounds with strong potential for the development of novel anti-inflammatory therapeutics.